单倍型造血干细胞移植后闭塞性细支气管炎综合征的临床分析

OBJECTIVE: To investigate the incidence, risk factors and survival of bronchiolitis obliterans syndrome (BOS) in patients who had undergone haplo-hematopoietic stem cell transplantation (haplo-HSCT). METHODS: This study retrospectively analyzed clinical data of 444 consecutive patients who underwent haplo-HSCT and survived at least 100 days after transplantation in the First Affiliated Hospital of Soochow University between January 2013 and December 2015. RESULTS: By the end of follow-up on January 1, 2018, 25 patients (5.63%) had BOS (BOS group). The median onset time of BOS was 448 (165–845) d post transplantation, the 1-year, 2-year and 3-year cumulative incidence of BOS was 1.6% (95%CI 1.5%–1.6%), 4.8% (95%CI 4.7%–4.8%) and 5.8% (95%CI 5.7%–5.8%), respectively. Among patients with chronic graft-versus-host disease (cGVHD), the cumulative incidence at the same intervals was 2.8% (95%CI 2.7%–2.8%), 9.5% (95%CI 9.4%–9.5%) and 11.5% (95%CI 11.4%–11.6%), respectively. In the multivariate analysis, the risk factors for BOS were high-risk primary disease, Ⅱ-Ⅳ aGVHD and preceding cGVHD with other organs. The 3-year overall survival (OS) was lower among patients with than those without BOS, but the difference was not significant [71.8% (95%CI 53.9%–89.6%) vs 72.4% (95%CI 68.1%–76.7%), P=0.400]. Overall 1-year, 3-year survival of patients with BOS from the time of diagnosis was 78.4% (95%CI 61.5%–95.3%) and 37.0% (95%CI 2.5%–71.5%), respectively, significantly less than those without (93.9% and 89.3%, from day 448 after transplantation, respectively, P<0.001). Furthermore, we found a significantly higher incidence of transplantation-related mortality (TRM) in patients with compared with patients without BOS (28.2% vs 10.9%, P<0.001). The main risk factor for OS of BOS patients was the severity of pulmonary impairment at the time of diagnosis. Patients who developed severe BOS had a worse OS than those with moderate and mild BOS (P=0.049). CONCLUSION: BOS is a severe pulmonary complication of haplo-HSCT. High-risk primary disease, Ⅱ-Ⅳ aGVHD and preceding cGVHD were independent risk factors for BOS. Patients who developed BOS had a worse OS than those without BOS. The main risk factor for OS of BOS patients was the severity of pulmonary impairment.